Development and Validation of a Virtual Endoluminal Surgery Simulator (VESS) for the Treatment of Colorectal Cancer Abstract Colorectal cancer (CRC) is the third most common cancer for both men and women in the United States and the second leading cause of cancer related deaths. However, early diagnosis and treatment are key factors to improve survival. In the US, a very active screening program using endoscopy is in place for CRC reduction. With advancement in interventional endoscopy, there is an increasing trend to resect colorectal polyp and early colorectal cancer endoscopically using small flexible tools advanced through the working channel of the endoscope. Endoscopic treatment is minimally invasive that offers certain advantages including faster recovery, shorter hospital stay, low cost and better postoperative quality of life compared with traditional intestinal surgery. Traditional polypectomy using a snare works well for pedunculated tumors (elongated tumors with a stalk), but not so much for sessile or flat tumors, which, unfortunately, carry a higher risk of cancer. For such tumors, the endoscopic mucosal resection (EMR) technique has been developed. However, for large tumors (>2cm) EMR carries risk of complications and complete clearance (en-bloc resection) may not be achievable leading to high risk of recurrence and residual tumor. Endoscopic Submucosal Dissection (ESD) is a technique that allows complete en-bloc resection and possible cure of tumors without size limitations, leading to precise histopathological margins and a much lower recurrence rate at long-term follow-ups. In this technique, which can be performed under mild sedation, a fluid is injected underneath the lesion and then a specialized knife is used to dissect the submucosa away. However, performing colorectal ESD is technically demanding since the colorectal wall is thin and constantly moving. Peristalsis can change the access to the lesion site and sharp bends can further limit access. Hence, a minimum of 50-100 cases are necessary to minimize incidence of intra-operative complications (e.g., bleeding and perforations) and attain basic proficiency. It is anticipated that a virtual reality (VR)-based trainer, with visual and haptic (touch) feedback, will be invaluable for training in ESD, allowing trainees to attain competence in a controlled environment with no risk to patients; customized learning; and real time feedback, mentoring and objective assessment. The goal of the present proposal is to design, develop and validate a Virtual Endoluminal Surgical Simulator (VESS) that can be used to train endoscopists in ESD. Such a simulator will have wider use in training of a variety of other submucosal surgical procedures (e.g., peroral endoscopic myotomy, endomicroscopy for the diagnosis of functional and motility disorders and peroral transgastric approaches to the peritoneum and mediastinum) which have been developed with a therapeutic intent other than the resection of tumors. A multidisciplinary team has been assembled to achieve the following Specific Aims: (SA 1) Design and develop a Virtual Endoluminal Surgical Simulator (VESS) platform for advanced therapeutic endoscopic procedures. Specifically, we will develop (1) physics-based computational models of human anatomy based upon in vivo experimental studies; and (2) haptic hardware interface. (SA 2) Develop training scenarios for endoscopic submucosal dissection (ESD) within the VESS with formative and summative performance feedback. Specifically, we will (i) integrate the computational models and in vivo experimental data from SA1 to develop a hands-on skill training environment for ESD which will allow the trainee to perform alternative approaches and encounter consequences of typical pitfalls and (ii) generate a performance feedback module for providing formative and summative feedback to the learner. (SA 3) Establish the validity of the VESS as a training tool by conducting experiments at Beth Israel Deaconess Medical Center with subjects voluntarily enrolled from local Boston medical schools and teaching hospitals to ensure that appropriate skills are being learnt on the VESS and performance measured on the VESS reflect the technical skills they intend to measure.